The ADVIA Centaur FT4 Immunoassay is for in vitro diagnostic use in the quantitative determination of free thyroxine (FT4) in serum or plasma (heparinized or EDTA) using the ADVIA Centaur and ADVIA Centaur XP Systems. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid diseases.

Device Description

The ADVIA Centaur FT4 assay is a competitive immunoassay using direct, chemiluminescent technology. Free thyroxine in the patient sample competes with acridinium ester-labeled T4 in the Lite Reagent for a limited amount of biotinylated polyclonal rabbit anti-T4 antibody that is bound to avidin that is covalently coupled to paramagnetic particles in the Solid Phase. There is an inverse relationship between the concentration of free thyroxine in the sample and relative light units (chemiluminescence).

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the ADVIA Centaur FT4 Immunoassay, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The provided document describes the performance characteristics without explicitly stating pre-defined "acceptance criteria" but rather demonstrates substantial equivalence to a predicate device. For the purpose of this analysis, we can infer acceptance criteria as demonstrating comparable performance to the predicate device within reasonable experimental variation.

Table of Acceptance Criteria (Inferred) and Reported Device Performance

Performance Characteristic	Inferred Acceptance Criteria (Comparable to Predicate Device)	ADVIA Centaur FT4 Performance (New Device)	Predicate Device (ACS:180 FrT4) Performance
Imprecision (Total CV%)	Comparable total CV% across various FT4 levels	0.37 ng/dL: 11.2%	0.58 ng/dL: 4.86%
		0.71 ng/dL: 4.85%	--
		1.31 ng/dL: 3.98%	1.42 ng/dL: 1.92%
		3.35 ng/dL: 4.07%	3.37 ng/dL: 3.55%
		5.32 ng/dL: 4.02%	--
		9.68 ng/dL: 6.53%	--
		(Study #2) 0.72 ng/dL: 4.16%
		(Study #2) 1.47 ng/dL: 4.58%
		(Study #2) 3.01 ng/dL: 4.44%
Specificity (% Cross Reactivity)	Very low cross-reactivity (<0.02%)	L-Triiodothyronine: <0.02%	Not explicitly stated for predicate
		Diiodotyrosine: <0.02%
		Monoiodotyrosine: <0.02%
		3,5-Diiodo-L-thyronine: <0.02%
		Reverse Triiodothyronine (rT3): <0.02%
Interfering Substances (% Change)	Minimal impact on FT4 concentrations (low % change)	Hemoglobin (300 mg/dL): -1.10% to -4.29%	Not explicitly stated for predicate
		Lipids (1000 mg/dL): 3.77% to 5.38%
		Bilirubin, free (20 mg/dL): 2.50% to 3.00%
		Bilirubin, conjugated (20 mg/dL): 2.50% to 5.10%
Method Comparison (Regression/r)	Strong correlation (high r-value, regression close to Y=X)	Serum vs. ACS:180 FrT4:
		N=283, Y=0.973x + 0.016, r=0.995
Serum / Plasma Equivalency (Regression/r)	Strong correlation between heparinized plasma, EDTA plasma, and serum	Heparinized Plasma vs. Serum:
		N=133, Y=0.979x + 0.058, r=0.997
		EDTA Plasma vs. Serum:
		N=108, Y=0.967x + 0.007, r=0.998

Study Details

Sample sizes used for the test set and the data provenance:
- Method Comparison (Serum vs. ACS:180 FrT4): N=283
- Serum / Plasma Equivalency (Heparinized Plasma vs. Serum): N=133
- Serum / Plasma Equivalency (EDTA Plasma vs. Serum): N=108
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is typical for such studies to use prospectively collected clinical samples or spiked samples, but this is not confirmed.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This device is an in vitro diagnostic (IVD) immunoassay measuring a biochemical marker (FT4 concentration) directly. The "ground truth" for the test set primarily relies on the results obtained from a legally marketed, predicate device (ACS:180 FrT4 Immunoassay) and established laboratory methods. It does not involve expert interpretation of images or clinical assessments in the way a diagnostic imaging AI would.
Adjudication method for the test set:
- Not applicable. Since the ground truth is established by quantitative measurement and comparison to a predicate device, there is no expert adjudication process involving multiple readers/interpreters.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is an IVD device for quantitative measurement of a biochemical marker, not a diagnostic imaging or interpretive AI device. Therefore, an MRMC study involving human readers is not applicable.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, effectively. The performance data presented (imprecision, specificity, interfering substances, correlation, serum/plasma equivalency) represents the standalone analytical performance of the ADVIA Centaur FT4 Immunoassay system. This is a "device only" performance evaluation without human interpretive intervention in the measurement process itself.
The type of ground truth used:
- The ground truth for evaluating the new device's analytical performance is primarily established by:
  - Measurements from a legally marketed predicate device: The ACS:180 FrT4 Immunoassay (K961510) served as the primary comparison for method correlation.
  - Known concentrations: For studies like specificity (cross-reactivity) and interfering substances, the "ground truth" involves starting with known concentrations of the analyte and interferents.
  - Internal standards (USP): The assay's standardization references an Internal Standard (USP), implying a traceable reference material for quantitative accuracy.
The sample size for the training set:
- Not applicable. This document describes an immunoassay (laboratory test), not a machine learning or AI algorithm in the context of "training data." The device's performance is based on its chemical and immunological design, not on being "trained" on a dataset in the AI sense.
How the ground truth for the training set was established:
- Not applicable. As stated above, this is not an AI/machine learning device that requires a training set with established ground truth. The assay's design and calibration are based on established scientific principles of immunoassay technology and reference materials.

Summary

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Koro167

510(k) Summary

AUG - 8 2008

Submitter informationContact person:	Philip Liu, Ph.D.Manager, Regulatory Affairs & Compliance
Address:	Siemens Healthcare Diagnostics511 Benedict AvenueTarrytown, NY 10591
Phone:	914-524-2443914-524-2500 (fax)
Date summary prepared:	July 10, 2008
Device Trade or Proprietary Names:	ADVIA Centaur FT4 Immunoassay
Device Common/Usual Name orClassification Name:	Free Thyroxine test system
Classification Number / Class:	21CFR 862.1695 / Class II

This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92.

The assigned 510(k) number is: K080167

Assay Predicate Device:

	Predicate Device
Device Name	ACS:180 Free T4 Assay
Common name	ACS FrT4
510(k) Number	K961510
Manufacturer	Siemens Healthcare Diagnostics(formerly Siemens Medical Solutions Diagnostics)

Device Description:

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paramagnetic particles in the Solid Phase. There is an inverse relationship between the concentration of free thyroxine in the sample and relative light units (chemiluminescence).

Statements of Intended Use:

Comparisons to the Predicate Device:

Assay Similarities

	ADVIA Centaur FT4 Assay(new device)	ACS:180 FrT4 Assay(predicate device)
Intended Use	For in vitro diagnostic use inthe quantitative determinationof free thyroxine (FT4) inserum or plasma	For in vitro diagnostic use inthe quantitative determinationof free thyroxine (FT4) inserum
Assay Method	Competitive immunoassay	Competitive immunoassay
Detection	Chemiluminescence	Chemiluminescence
Assay Range	0.1 - 12.0 ng/dL	0.1 - 12.0 ng/dL
Calibrators	Calibrator A	Calibrator A
Calibration	2 point	2 point
Reagents	Two liquid reagents, ready touse	Two liquid reagents, ready touse
Lite Reagent	Acridium ester labeled T4	Acridium ester labeled T4
ExpectedValues(ng/dL)	Euthyroid 0.89 - 1.76Hypothyroid < 0.89Hyperthyroid >1.76	Euthyroid 0.89 - 1.76Hypothyroid < 0.89Hyperthyroid >1.76
Standardization	Internal Standard (USP)	Internal Standard (USP)

Assay Differences

	ADVIA Centaur FT4 Assay(new device)	ACS:180 FrT4 Assay(predicate device)
Specimen Type	Human serum or plasma(heparinized or EDTA)	Human serum
Solid PhaseReagent	Biotin-labeled polyclonal anti-T4 bound to avidinparamagnetic particles	Polyclonal anti-T4 bound toparamagnetic particles

Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) ADVIA Centaur Free T4 Premarket Notification 510(k) 510(k) Summary (Revised, July 2008)

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Performance:

Substantial equivalence was demonstrated by testing several method performance characteristics including imprecision, method comparison, interfering substances, and specificity. The following tables summarize the precision (total), interfering substances, specificity, serum / plasma equivalency and method comparison results.

All of the evaluation studies gave acceptable results compared to the predicate device. These studies support that the ADVIA Centaur FT4 immunoassay is substantially equivalent to the ACS:180 FrT4 immunoassay that is currently marketed.

Imprecision

ADVIA Centaur FT4		ACS:180 FrT4
Level (ng/dL)	Total CV (%)	Level (ng/dL)	Total CV (%)
0.37	11.2	0.58	4.86
0.71	4.85	--	--
1.31	3.98	1.42	1.92
3.35	4.07	3.37	3.55
5.32	4.02	--	--
9.68	6.53	--	--

ADVIA Centaur FT4
Level (ng/dL)	Total CV (%)
0.72	4.16
1.47	4.58
3.01	4.44

Study #2 - Multiple reagent lots, multiple systems

Specificity

The cross-reactivity of the ADVIA Centaur FT4 assay with a substance can be expressed as the ratio of:

• the amount of T4 required to displace 50% of the maximally bound labeled T4 from the anti-T4 antibody,

· the amount of the cross-reactant to give the same 50% displacement

Cross Reactant	% Cross Reactivity
L-Triiodothyronine	<0.02%
Diiodotyrosine	<0.02%
Monoiodotyrosine	<0.02%
3,5-Diiodo-L-thyronine	<0.02%
Reverse Triiodothyronine (rT3)	<0.02%

Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) ADVIA Centaur Free T4 Premarket Notification 510(k) 510(k) Summary (Revised, July 2008)

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Interfering Substances

Interfering Substance	Interferent Conc.(mg/dL)	FT4 conc.(ng/dL)	Effect(% change)
Hemoglobin	300	0.90	-1.10
Hemoglobin	300	1.34	-4.29
Lipids (Intralipids)	1000	1.10	3.77
Lipids (Intralipids)	1000	1.37	5.38
Bilirubin, free	20	1.03	3.00
Bilirubin, free	20	1.23	2.50
Bilirubin, conjugated	20	1.03	5.10
Bilirubin, conjugated	20	1.23	2.50

Correlation

(y = ADVIA Centaur FT4, x = comparison method/system)

Specimen type,System (y)	Comparison System (x)	N	Regression Equation	r	Sample Range(ng/dL)
Serum, ADVIACentaur FT4	Serum, ACS:180 FrT4	283	$Y = 0.973 x + 0.016$	0.995	0.14 - 11.1

Serum / Plasma (Lithium heparin and EDTA)

Specimen type (y)	Comparison System (x)	N	Regression Equation	r	Sample Range (ng/dL)
Heparinized Plasma	Serum	133	$Y = 0.979x + 0.058$	0.997	0.17 – 11.4
EDTA Plasma	Serum	108	$Y = 0.967x + 0.007$	0.998	0.17 – 11.4

Conclusions:

The Siemens Healthcare Diagnostics ADVIA Centaur FT4 immunoassay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens Healthcare Diagnostics ACS:180 FrT4 immunoassay (K961510).

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three stripes representing the three levels of government: federal, state, and local. The eagle is encircled by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics c/o Philip Liu, Ph.D. Manager, Regulatory Affairs & Compliance 511 Benedict Avenue Tarrytown. NY 10591

AUG - 8 2008

Re: K080167 Trade Name: ADVIA Centaur FT4 Immunoassay Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: Class II Product Codes: CEC Dated: June 16, 2008 Received: June 17, 2008

Dear Dr. Liu:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to 1egally marketed predicate device results in a classification for your device and thus, permits vour device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll the from the (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yéan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K080167

Device Name: ADVIA Centaur FT4 Immunoassay

Indications For Use:

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson
Division Sign Off

Division Sign-Off

e of In Vitro Diagnostic Device Evaluation and Saf

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Regulation Number and Section

§ 862.1695 Free thyroxine test system.

(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.